Synthesis and properties of pyrimido[4,5-<Emphasis Type="Italic">a</Emphasis>]- and pyrido[4,3-<Emphasis Type="Italic">a</Emphasis>]carbazole derivatives

Methods for the synthesis of substituted pyrimido [4,5-a]- and pyrido[4,3-a]carbazoles were proposed. Condensation of 2-(dimethylaminomethylene)-6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one with guanidine and thiourea afforded 2-amino-8-methyl-6,11-dihydro-5H-pyrimido[4,5-a]carbazole and 8-methyl-3,5,6,11-tetrahydro-2H-pyrimido[4,5-a]carbazole-2-thione, respectively. The reaction of cyano(6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-ylidene)acetamide with dimethylformamide dimethyl acetal gave N-(dimethylamino-methylene)cyano(6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-ylidene)acetamide. Cyclization of the latter yielded 1-cyano-8-methyl-3,5,6,11-tetrahydro-2H-pyrido[4,3-a]carbazol-2-one.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2740–2744, December, 2004.     

Stereoselective synthesis of 4-substituted 1,2,3,4,10,10a-hexahydropyrazino[1,2-<Emphasis Type="Italic">a</Emphasis>]indoles

4-Substituted 1,2,3,4-tetrahydropyrazino[1,2-a]indoles were synthesized from 2-cyanoindole. (R)-4-Methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole was obtained by the Mitsunobu reaction. Stereoselective reduction of 4-substituted 1,2,3,4-tetrahydropyrazino[1,2-a]indoles gave 4-substituted 1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles. (4R, 10aR)-4-Methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole was synthesized.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 221–225, January, 2005.     

Synthesis of new 1<Emphasis Type="Italic">H</Emphasis>-pyridazine derivatives <Emphasis Type="Italic">peri</Emphasis>-annelated with acenaphthene and acenaphthylene

The reaction of 6-acetyl-5-hydroxyacenaphthene with methylhydrazine afforded 1,3-dimethyl-1H-6,7-dihydroacenaphtho[5,6-de]pyridazine. Its dehydrogenation with chloranil gave 1,3-dimethyl-1H-acenaphtho[5,6-de]pyridazine, which is a heteroaromatic compound with an essentially new topology of the ρsystem. The reaction of 3-methyl-1H-6,7-dihydroacenaphtho[5,6-de]pyridazine with 3,5-di-tert-butyl-1,2-benzoquinone yielded a dimer containing the acenaphthene and acenaphthylene moieties of peri-annelated 1H-1,2-diazines connected in positions 1′ and 9.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 777–780, March, 2005.     

Reaction of 2-methoxy-1,3,2-dioxaphosphorino[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-4(4<Emphasis Type="Italic">H</Emphasis>)-one with hexafluoroacetone

The reaction of the di-O-trimethylsilyl derivative of 2-hydroxynicotinic acid with methyl phosphodichloridite afforded 2-methoxy-1,3,2-dioxaphosphorino[4,5-b]pyridin-4(4H )-one. The NMR spectrkscopic data suggest that the reaction of the latter with hexafluoroacetone produces unstable 2-methoxy-2,5-dioxo-4,4-bis(trifluoromethyl)-4,5-dihydro-1,3,2-dioxaphosphepino[4,5-b]pyridine, which is readily transformed into 9-methyl-2,5-dioxo-4,4- bis(trifluoromethyl)-4,5-dihydro-1,3,2-dioxaphosphepino[4,5-b]pyrid-9-inium-2-oate. The structure of the hydrolysis product of the latter, viz., 1-methyl-3-(2-hydroxy-3,3,3-trifluoro-2- trifluoromethylpropanoyl)pyridin-2-one, was established by X-ray diffraction analysis.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1640–1646, August, 2004.     

Synthesis of 6-aryl-1,6-dihydrodipyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>:4,3-<Emphasis Type="Italic">c</Emphasis>]pyridines

6-Azido-1H-pyrazolo[3,4-b]pyridino-5-carbaldehydes react with aromatic amines to give the corresponding N-arylimines which cyclize on heating in boiling toluene to give 6-aryl-1,6-dihydrodipyrazolo[3,4-b:4,3-e]pyridines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, 1717–1722, November, 2004.     

Alternative Routes to the Pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>][1,2,4]triazolo-[1,5-<Emphasis Type="Italic">c</Emphasis>]pyrimidine System

Formimidic acid esters derived from 1-substituted 5-aminopyrazole-4-carbonitriles reacted with carboxylic acid hydrazides on heating to give 2,7-disubstituted pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives as a result of double heterocyclization. The same compounds were obtained by thermal recyclization of 1-aroyl-2-(1-R-pyrazolo[3,4-d]pyrimidin-4-yl)hydrazines.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 6, 2005, pp. 934–938.Original Russian Text Copyright © 2005 by Tyurin, Vorob’ev, Minyaeva, Krasnikov, Mezheritskii.     

Reductive Acylamination of Pyridine <Emphasis Type="Italic">N</Emphasis>-Oxide with Aminopyridines and Their <Emphasis Type="Italic">N</Emphasis>-<Emphasis Type="Italic">p</Emphasis>-Tolylsulfonyl Derivatives

Pyridine N-oxide reacts with 2- and 3-aminopyridines and their N-p-tolylsulfonyl derivatives in alkaline medium in the presence of p-toluenesulfonyl chloride to give N-p-tolylsulfonyl-2,2′- and 2,3′-dipyridylamines, respectively, as a result of reductive acylamination. In the reactions with 4-aminopyridine and 4-p-tolylsulfonyl-aminopyridine, their N-p-tolylsulfonyl- and N,N-bis(p-tolylsulfonyl) derivatives are formed, while reductive acylamination does not occur.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 128–130.Original Russian Text Copyright © 2005 by Solekhova, Kurbatov.     

Halogenation of Imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-one Derivatives

Chlorination and bromination of 2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one and its N-methyl-substituted derivatives in acetic acid at 90–95°C leads to formation of the corresponding 5,6-dichloro(dibromo)-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones. Iodination of the same substrates with ICl under analogous conditions yields 6-iodo derivatives. Chlorination of 6-iodo-1,3-dimethyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one is accompanied by replacement of the iodine atom by chlorine with formation of 5,6-dichloro-1,3-dimethyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one. Bromination of 6-bromo- and 6-chloro-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones gives 5,6-dibromo- and 5-bromo-6-chloro-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones, respectively.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 4, 2005, pp. 586–589.Original Russian Text Copyright © 2005 by Yutilov, Lopatinskaya, Smolyar, Gres’ko.     

Synthesis of 1,4-Dihydropyrano[2,3-<Emphasis Type="Italic">c</Emphasis>]pyrazole Derivatives

In reaction of 2-(2-thienyl)- and 2-(2-furyl)acrylonitriles with 3-methyl-1-phenyl-5-pyrazolone in the presence of basic catalysts 4-thienyl- and 4-furyl derivatives of 3,5-dimethyl-1,7-diphenyl-4,8-dihydropyrano-[2,3-c, 5,6-c]dipyrazole were obtained.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005, pp. 756–758.Original Russian Text Copyright © 2005 by Vasyun’kina, Bykova, Plotkin, Ramsh.     

2-Alkyl-4-oxohexahydropyrimido[4,5-<Emphasis Type="Italic">d</Emphasis>]- and -[5,4-<Emphasis Type="Italic">d</Emphasis>]azocines

It has been established that 2-R-4-oxotetrahydropyrido[4,3-d]pyrimidines, under the action of activated alkynes in methanol, form a mixture of 2-R-4-oxohexahydropyrimido[4,5-d]azocines and products of decomposition of the tetrahydropyridine ring, the 2-R-5-methoxymethyl-4-oxo-6-vinylaminoethyl-pyrimidines. Tetrahydropyrido[3,4-d]pyrimidine, isomeric at the junction of the pyrimidine and tetrahydropyridine rings, forms only the corresponding pyrimido[5,4-d]azocine, the product of expansion, under the action of methyl propiolate.     

Acylation of 6,7,8,9-tetrahydro-5<Emphasis Type="Italic">H</Emphasis>-[1,2,4]triazolo-[4,3-<Emphasis Type="Italic">a</Emphasis>]azepin-3-ylacetonitrile

6,7,8,9-Tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-3-ylacetonitrile reacts with carboxylic acid anhydrides and chlorides to afford acylation products at the nitrogen atom in the heteroring or methylene carbon atom, depending on the conditions and nature of the acylating agent. Heating of the N-acyl derivatives leads to migration of the acyl group with formation of C-acyl derivatives.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 12, 2004, pp. 1858–1860.Original Russian Text Copyright © 2004 by Makei, Volovenko, Nazarenko, Tolmachev.     

Annelation of drotaverine by <Emphasis Type="Italic">p</Emphasis>-quinones to form hydroxyindolo- and hydroxybenzindoloisoquinoline derivatives

1-(3, 4-Diethoxybenzyl)-6, 7-diethoxy-3, 4-dihydroisoquinoline (drotaverine, 1a) reacts with p-benzoquinone (2) and p-naphthoquinone (3) in nitromethane or during fusion to give 5-(3, 4-diethoxyphenyl)-7, 8-diethoxy-3-hydroxy-5a, 10, 11, 12-tetrahydroindolo[2, 1-a]isoquinoline (4) and 7-(3, 4-diethoxyphenyl)-9, 10-diethoxy-5-hydroxy-7a, 12, 13, 14-tetrahydrobenz[g]indolo[2, 1-a]isoquinoline (5), respectively. Compounds 4 and 5 are smoothly alkylated at the oxygen atom in the presence of bases. The structure of one alkylation product, viz., 3-allyloxy-5-(3, 4-diethoxyphenyl)-7, 8-diethoxy-5a, 10, 11, 12-tetrahydroindolo[2, 1-a]isoquinoline, was established by X-ray diffraction analysis.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 761–769, March, 2005.     

Synthesis of 8,8-R,R-8,9-dihydro[1,2,4]triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]quinazolin-6(7<Emphasis Type="Italic">H</Emphasis>)-ones

Three-component condensation of 3-amino-1,2,4-triazole (or its 5-methyl and 5-methylthio derivatives), dimedone (or cyclohexane-1,3-dione), and dimethylformamide dimethyl acetal afforded 8,8-R, R-8,9-dihydro[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-ones. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2805–2807, December, 2005.     

Spiropyrans and spirooxazines. 3. Synthesis of photochromic 5′-(4,5-diphenyl-1,3-oxazol-2-yl)-spiro[indoline-2,3′-naphtho[2,3-<Emphasis Type="Italic">b</Emphasis>]pyran]

The reaction of 2-hydroxy-3-(4,5-diphenyl-1,3-oxazol-2-yl)-1-naphthaldehyde with 1,2,3,3-tetramethyl-3H-indolium perchlorate afforded photochromic spiro[indoline-2,3′-naphthopyran] containing a 4,5-diphenyloxazole group in position 5′ of the naphthopyran fragment. The merocyanine form of the spiropyran gave complexes with bivalent heavy cations.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 693–697, March, 2005.     

Synthesis of substituted benz[<Emphasis Type="Italic">g</Emphasis>]indole-6,9-diones and benzo[<Emphasis Type="Italic">h</Emphasis>]quinoline-7,10-diones by heterocyclization of 6-alkynyl-5-amino-1,4-naphthoquinones

Substituted benz[g]indole-6,9-diones were synthesized by intramolecular cyclization of 6-alkynyl-5-amino-3-diethylamino-1,-4-naphthoquinones. A method was developed for the preparation of 2-aryl(or alkyl)-4,9-bis(dialkylamino)benzo[h]quinoline-7,10-diones, which involves the addition of a secondary amine to 6-acylethynyl-5-amino-3-diethylamino-1,-4-naphthoquinone followed by cyclization of the resulting adduct.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 412–418, February, 2005.     

Xylogranatinin,a new pyrido[1, 2-<Emphasis Type="Italic">a</Emphasis>]pyrazine alkaloid from the fruit of a Chinese mangrove <Emphasis Type="Italic">Xylocarpus granatum</Emphasis>

9-Hydroxy-3-methoxy-6H-pyrido[1,2-a]pyrazin-6-one, a new pyrido[1,2-a]pyrazine alkaloid named xylogranatinin, was isolated from the fruit of a Chinese mangrove Xylocarpus granatum. Its structure was elucidated on the basis of spectroscopic data, especially 2D NMR techniques including HSQC and HMBC. To the best of our knowledge, this is the first time that a pyrido[1,2-a]pyrazine alkaloid was found as a natural product. Published in Khimiya Prirodnykh Soedinenii, No. 4, pp. 351–352, July–August, 2007.     

Synthesis and Reactions of 5-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-7-phenyl-7<Emphasis Type="Italic">H</Emphasis>-thiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine-6-carbonitrile

Summary. 5-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-7-phenyl-7H-thiazolo[3,2-a]pyrimidine-6-carbonitrile was synthesized via the reaction of 4-(2-aminothiazol-4-yl)-3-methyl-1-phenyl-2-pyrazolin-5-one with benzylidene malononitrile and was then transformed to related fused heterocyclic systems. The antifungal and antibacterial studies revealed in some cases excellent biocidal properties.     

Fluorine-containing pyrido[1,2-<Emphasis Type="Italic">a</Emphasis>]quinazolin-6-ones

Reactions of 2-aminopyridine and 2-amino-5-methylpyridine with 2,3,4,5-tetrafluorobenzoyl chloride afforded N,N’-diaroylpyridinium salts, which were converted into 6H-pyrido[1,2-a]quinazolin-6-ones by refluxing in toluene in the presence of triethylamine. The angular structure of the tricyclic derivatives obtained was confirmed by ¹⁹F and ¹³C NMR spectroscopy and 2D heteronuclear HetCOR and HMBC experiments.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2216–2220, October, 2004.     

Structure and photochromism of 2-(<Emphasis Type="Italic">N</Emphasis>-acyl-<Emphasis Type="Italic">N</Emphasis>-arylaminomethylene)benzo[<Emphasis Type="Italic">b</Emphasis>]thiophen-3(2<Emphasis Type="Italic">H</Emphasis>)-ones

It was shown by electron absorption spectroscopy and X-ray diffraction analysis that steric strains in photochromic 2-(N-acyl-N-arylaminomethylene) benzo[b]thiophen-3(2H)-one molecules ortho-substituted in the N-phenyl ring increase the quantum yield of the N→O photoinduced rearrangement in accord with an increase in the steric constant of the ortho-substituent.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2151–2155, October, 2004.     

Reactions of 3-allyl-4-oxothieno[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-2-yl disulfides with iodine

Reactions of 3-allyl-4-oxothieno[2,3-d]pyrimidin-2-yl disulfides with iodine afforded 2-iodomethyl-2,3-dihydrothieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidin-5-ones. A probable mechanism of this transformation was theoretically justified. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2501–2504, November, 2005.